ACE2 contributes to the maintenance of mouse epithelial barrier function

Area of Science:

• Gastroenterology
• Molecular Biology
• Immunology

Background:

• The coronavirus disease-19 (COVID-19) pandemic highlighted the importance of angiotensin I converting enzyme 2 (ACE2), the viral entry receptor.
• ACE2 is highly expressed in the gut, but its precise role in intestinal homeostasis remains incompletely understood.
• Understanding ACE2's function in the gut is critical for developing safe COVID-19 treatments and exploring therapeutic alternatives.

Purpose of the Study:

• To investigate the role of ACE2 in intestinal stemness and gut homeostasis.
• To determine the impact of ACE2 deficiency on intestinal barrier function and susceptibility to inflammatory bowel disease (IBD).

Main Methods:

• Utilized Ace2 knockout mice and isolated intestinal organoids to study ACE2 function.
• Established an inflammatory bowel disease (IBD) mouse model using dextran sodium sulfate.
• Quantified intestinal stem cell markers (LGR5, KI67) and assessed intestinal barrier integrity via FITC-dextran 4 (FD-4) assay.

Main Results:

• ACE2 expression was confirmed in the colon via Western blotting, immunofluorescence, and RT-PCR.
• Ace2 knockout organoids exhibited reduced LGR5 and KI67 levels, increased calcium concentration, and heightened permeability.
• Ace2 knockout mice showed increased susceptibility to IBD, characterized by earlier onset of bloody stool, compromised intestinal architecture, and significant weight loss.

Conclusions:

• ACE2 plays a significant role in promoting intestinal stem cell proliferation.
• ACE2 is essential for orchestrating mucosal homeostasis in the gut.
• Targeting ACE2 may offer potential therapeutic strategies for gastrointestinal disorders.